Pinpointing the potential hits for hindering interaction of SARS-CoV-2 S-protein with ACE2 from the pool of antiviral phytochemicals utilizing molecular docking and molecular dynamics (MD) simulations

Abstract

SARS-CoV-2, the viral particle, is responsible for triggering the 2019 Coronavirus disease outbreak (COVID-19). To tackle this situation, a number of strategies are being devised to either create an antidote, a vaccine, or agents capable of preventing its infection. To enable research on these strategies, numerous target proteins are identified where Spike (S) protein is presumed to be of immense potential. S-protein interacts with human angiotensin-converting-enzyme-2 (ACE2) for cell entry. The key region of S-protein that interacts with ACE2 is a portion of it designated as a receptor-binding domain (RBD), following whereby the viral membrane fuses with the alveolar membrane to enter the human cell. The proposition is to recognise molecules from the bundle of phytochemicals of medicinal plants known to possess antiviral potentials as a lead that could interact and mask RBD, rendering them unavailable to form ACE2 interactions. Such a molecule is called the 'S-protein blocker’. A total of 110 phytochemicals from Withania somnifera , Asparagus racemosus, Zinziber officinalis , Allium sativum , Curcuma longa and Adhatoda vasica were used in the study, of which Racemoside A, Ashwagandhanolide, Withanoside VI, Withanoside IV and Racemoside C were identified as top five hits using molecular docking. Further, essential Pharmacophore features and their ADMET profiles of these compounds were studied following to which the best three hits were analyzed for their interaction with RBD using Molecular Dynamics (MD) simulation. Binding free energy calculations were performed using MM/GBSA, proving these phytochemicals can serve as S-protein blocker.

Identification of antiviral phytochemicals as a potential SARS-CoV-2 main protease (Mpro) inhibitor using docking and molecular dynamics simulations

“…A library of 110 natural compounds with experimental antiviral properties were manually compiled from literature with special emphasis on plants including Withania somnifera, Asparagus racemosus , Zinziber officinalis, Allium sativum, Curcuma longa, and Adhatoda vasica 39 – 41 . The 3D structure of these natural compounds was retrieved from the NCBI PubChem database or by drawing the structure using a MarvinSketch 20.20.1 (ChemAxon, LLC) drawing tool if unavailable.…”

Ayurveda Rasayana as antivirals and immunomodulators: potential applications in COVID-19

“…( Yashtimadhu ) Kalhor et al ( 2020 ) Spike protein Phyllaemblicin G7 Phyllanthus emblica L. ( Aamlaki ) Ilona et al ( 2011 ) Racemoside A, racemoside C, asparoside-C, asparoside-F Asparagus racemosus Willd. ( Shatavari ) Chikhale et al ( 2020 ); Patel et al ( 2021 ) Glycyrrhizic acid Glycyrrhiza glabra L . ( Yashtimadhu ) Sinha et al ( 2020 ) Withaferin Withania somnifera (L.) Dunal ( Ashwagandha ) Straughn and Kakar ( 2020 ) Withanolide M Withania somnifera (L.) Dunal ( Ashwagandha ) Khanal et al ( 2021 ) Helicase inhibitors Phyllaemblicin B Phyllaemblinol Phyllanthus emblica L. ( Aamlaki ) Ilona et al ( 2011 ) …”

“…In another in silico study, natural steroidal saponins racemoside A and racemoside C interact with RBD of S-protein and inhibit its interaction with ACE2, ultimately blocking the entry of viral particle into the human host. It interact with S-protein and other structural proteins of SARS-CoV-2 (Patel et al 2021 ). As far as the toxicity is concerned, the aqueous extract of the roots of A. racemosus has been reported for diuretic activity at the highest dose of 3200mg/kg without any acute toxicity (Kumar et al 2010 ).…”

Evaluation of botanicals as potential COVID-19 symptoms terminator

“…W. somnifera components withanolides have potential antiviral properties on COVID-19[ 49 ]. Patel et al [ 50 ] demonstrated that W. somnifera 's Withanoside VI components have positive interactions at the binding site of protein targets of SARS-CoV-2. Withanone reduced the electrostatic interaction between ACE2 and receptor binding domain[ 51 ].…”